In the orthopedic and periodontal surgical fields it is highly desirable to find efficient systems for treating patients with skeletal disorders and deformations, including the repairing of large bone defects originating from trauma, excision of tumors and congenital malformations, reconstructing bone stocks worn off by an implanted endoprothesis in revision operations and healing delayed or non-united fractures.
The autologous graft (“autograft”) is the traditional approach to bone repair, but the harvesting of bone grafts can lead to complications, such as bleeding, pain, and infection. Autografts have also limited availability thus, as an alternative, many inorganic materials are used. Calcium phosphates such as hydroxyapatite (HAP) and tricalcium phosphates (TCP) and their variations are commonly known bone substitute materials. These materials provide an osteoconductive scaffold to new bone forming.
The bioactivity of inorganic materials can be increased by adding osteogenic stimulus to the bone graft extender. Allografts, demineralised bone matrices (DBM) and native bone extracts have been shown to increase bone healing capacity and enhance integration in many different studies. Combinations of bovine bone-derived growth factors in collagen and DBM or coralline HAP carriers have been shown to be as good as iliac crest autografts when studied as fusion rates in spinal arthrodesis in rabbits and monkeys.
Commercially available synthesized biomaterials have been developed and can be used as filling material or inlay as well as onlay support. Unfortunately, these materials lack the biological activity needed to initiate bone regeneration. Synthetic carriers prepared from such materials including polylactic acids and hyaluronic acids are described e.g. in the patent U.S. Pat. No. 5,366,508. Bone morphogenetic protein (BMP) is considered an important factor in osteogenic devices and participates actively in the implantation process.
EP 0 883 410 B1 discloses a method for producing the modified bone morphogenetic protein (BMP) complex for an osteogenic device wherein the modified BMP complex is obtainable by a method comprising the steps of (a) pulverizing demineralized bone material; (b) extracting the bone material in step (a) with guanidinium hydrochloride (GuHCl); (c) performing a filtration using a tangential flow system; (d) performing a gel filtration by which a partially purified BMP complex demonstrating three peaks comprising three protein fractions, which are characterized by having different molecular weights, Fraction I being a high MW (100-700 kD) protein with osteoinductive BMP activity, Fraction II being a medium MW (25-55 kD) immunogenic protein lacking BMP activity and Fraction III being a low MW (15-25 kD) protein with osteoinductive BMP activity is obtainable; and (e) removing from the partially purified BMP a protein fraction with immunogenic and inflammatory properties having a MW of 25-55 kD as determined by gel filtration.
The need for more osteogenic materials that are useful for a variety of bone repair applications, especially, materials that are compatible with the carrier materials typically used in the applications described above, is manifest.